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Variants near the gene TRIB1 are significantly associated with several plasma lipid traits, circulating liver enzymes, and the development of coronary artery disease in humans; however, it is not clear how its protein product tribbles-1 regulates lipid metabolism. Here, we evaluated mice harboring a liver-specific deletion of Trib1 (Trib1_LSKO) to elucidate the role of tribbles-1 in mammalian hepatic lipid metabolism. These mice exhibited increased hepatic triglyceride (TG) content, lipogenic gene transcription, and de novo lipogenesis. Microarray analysis revealed altered transcription of genes that are downstream of the transcription factor C/EBPÎ±, and Trib1_LSKO mice had increased hepatic C/EBPÎ± protein. Hepatic overexpression of C/EBPÎ± in WT mice phenocopied Trib1_LSKO livers, and hepatic knockout of Cebpa in Trib1_LSKO mice revealed that C/EBPÎ± is required for the increased lipogenesis. Using ChIP-Seq, we found that Trib1_LSKO mice had increased DNA-bound C/EBPÎ± near lipogenic genes and the Trib1 gene, which itself was transcriptionally upregulated by C/EBPÎ± overexpression. Together, our results reveal that tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPÎ±, which in turn transcriptionally upregulates Trib1. These data suggest an important role for C/EBPÎ± in mediating the lipogenic effects of hepatic Trib1 deletion and provide insight into the association between TRIB1 and plasma lipids, and liver traits in humans.

Is Prebiopsy MRI Good Enough to Avoid Prostate Biopsy? A Cohort Study Over a 1-Year Period. - Clinical genitourinary cancer

An Umpolung Approach for the Chemoselective Arylation of Selenocysteine in Unprotected Peptides. - Journal of the American Chemical Society

Herein we report an umpolung strategy for the bioconjugation of selenocysteine in unprotected peptides. This mild and operationally simple approach takes advantage of the electrophilic character of an oxidized selenocysteine (Se-S bond) to react with a nucleophilic arylboronic acid to provide the arylated selenocysteine within hours. This reaction is amenable to a wide range of boronic acids with different biorelevant functional groups and is unique to selenocysteine. Experimental evidence indicates that under oxidative conditions the arylated derivatives are more stable than the corresponding alkylated selenocysteine.

Informed consent is an ethical process for ensuring patient autonomy. Multimedia presentations (MMPs) often aid the informed consent process for research studies. Thus, it follows that MMPs would improve informed consent in clinical settings.The aim of this study was to determine if an MMP for the informed consent process for ketamine sedation improves parental satisfaction and comprehension as compared with standard practice.This 2-phase study compared 2 methods of informed consent for ketamine sedation of pediatric patients. Phase 1 was a randomized, prospective study that compared the standard verbal consent to an MMP. Phase 2 implemented the MMP into daily work flow to validate the previous year's results. Parents completed a survey evaluating their satisfaction of the informed consent process and assessing their knowledge of ketamine sedation. Primary outcome measures were parental overall satisfaction with the informed consent process and knowledge of ketamine sedation.One hundred eighty-four families from a free-standing, urban, tertiary pediatric emergency department with over 85,000 annual visits were enrolled. Different demographics were not associated with a preference for the MMP or improved scores on the content quiz. Intervention families were more likely "to feel involved in the decision to use ketamine" and to understand that "they had the right to refuse the ketamine" as compared with control families. The intervention group scored significantly higher overall on the content section than the control group. Implementation and intervention families responded similarly to all survey sections.Multimedia presentation improves parental understanding of ketamine sedation, whereas parental satisfaction with the informed consent process remains unchanged. Use of MMP in the emergency department for informed consent shows potential for both patients and providers.

A meta-analysis of randomized double-blind clinical trials in CMT1A to assess the change from baseline in CMTNS and ONLS scales after one year of treatment. - Orphanet journal of rare diseases

CMT1A is the most common inherited peripheral neuropathy. There is currently no approved treatment. We performed a meta-analysis including four randomized, double-blind, Placebo-controlled clinical trials to assess the disease progression after one year under Placebo, Ascorbic Acid (AA) or PXT3003, a combination of three repurposed drugs. We observed a weak deterioration in patients under Placebo, well below the reported natural disease progression. Patients treated with AA were stable after one year but not significantly different from Placebo. Patients undergoing PXT3003 treatment showed an improvement in CMTNS and ONLS, statistically significant versus Placebo and potentially precursory of a meaningful change in the disease course.

A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline hyperlipidemic individuals. - Lipids in health and disease

Circulating levels of triacylglycerol (TG) is a recognized risk factor for developing cardiovascular disease, a leading cause of death worldwide. The Institute of Medicine and the American Heart Association both recommend the consumption of n-3 polyunsaturated fatty acids (PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to reduce serum TG in hyperlipidemic individuals. Additionally, a number of systematic reviews have shown that individuals with any degree of dyslipidemia, elevated serum TG and/or cholesterol, may benefit from a 20-30% reduction in serum TG after consuming n-3 PUFA derived from marine sources. Given that individuals with serum lipid levels ranging from healthy to borderline dyslipidemic constitute a large portion of the population, the focus of this review was to assess the potential for n-3 PUFA consumption to reduce serum TG in such individuals. A total of 1341 studies were retrieved and 38 clinical intervention studies, assessing 2270 individuals, were identified for inclusion in the current review. In summary, a 9-26% reduction in circulating TG was demonstrated in studies where â‰¥ 4 g/day of n-3 PUFA were consumed from either marine or EPA/DHA-enriched food sources, while a 4-51% reduction was found in studies where 1-5 g/day of EPA and/or DHA was consumed through supplements. Overall, this review summarizes the current evidence with regards to the beneficial effect of n-3 PUFA on circulating TG levels in normolipidemic to borderline hyperlipidemic, otherwise healthy, individuals. Thus demonstrating that n-3 PUFA may play an important role in the maintenance of cardiovascular health and disease prevention.

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